title: Paradoxical oncogenesis: are all BRAF inhibitors equal?
abstract: Cutaneous squamous cell carcinoma (cSCC) is a concerning toxicity with BRAF inhibitors in the treatment for melanoma. While the two drugs shown to improve survival, vemurafenib, and dabrafenib, have similar efficacy, the reported rates of cSCC are quite different. Drawing upon preclinical and clinical trial data, this article discusses the potential factors behind the different cSCC incidences reported with the two BRAF inhibitors and provides a strategic approach to understand this issue further.
authors.affiliation: Melanoma Institute Australia, Sydney, NSW, Australia. alexander.menzies@sydney.edu.au
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Menzies
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
mesh_terms: D063646:Carcinogenesis / Q000187:drug effects* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
keywords: BRAF inhibitor; dabrafenib; melanoma; secondary malignancy; squamous cell carcinoma; vemurafenib